Src activation in the induction of long-term potentiation in CA1 hippocampal neurons.
Long-term potentiation (LTP) is an activity-dependent strengthening of synaptic efficacy that is considered to be a model of learning and memory. Protein tyrosine phosphorylation is necessary to induce LTP. Here, induction of LTP in CA1 pyramidal cells of rats was prevented by blocking the tyrosine kinase Src, and Src activity was increased by stimulation producing LTP. Directly activating Src in the postsynaptic neuron enhanced excitatory synaptic responses, occluding LTP. Src-induced enhancement of alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) receptor-mediated synaptic responses required raised intracellular Ca2+ and N-methyl-D-aspartate (NMDA) receptors. Thus, Src activation is necessary and sufficient for inducing LTP and may function by up-regulating NMDA receptors.
Lu
Y M
YM
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Department of Molecular and Medical Genetics, University of Toronto, M5S 1A8, Canada.
Roder
J C
JC
Davidow
J
J
Salter
M W
MW
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D004789:Enzyme Activation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000494:pharmacology; D017966:Pyramidal Cells / Q000201:enzymology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation; D019061:src-Family Kinases / Q000378:metabolism*
D009842:Oligopeptides; D010446:Peptide Fragments; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases; D002118:Calcium